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Small Bowel Transplantation in Sensitized Recipients: Comparison with Heart, Kidney, and Liver Grafts

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Small Bowel Transplantation in Sensitized Recipients: Comparison with Heart, Kidney, and Liver Grafts Small Bowel Transplantation in Sensitized Recipients: Comparison with Heart, Kidney, and Liver Grafts N. Murase. S. Fujisaki. M. Tanabe, A.C. Tsamandas, S. Todo, T.E. Starzl. and A.J. Demetris MALL BOWEL transplantation in humans. alone or was congestion of capillaries in the lamina propria. sub­ S in combination with other viscera. has been per­ mucosa. and inside the Peyer's patches, with diffuse formed frequently using FK506 immunosuppression. and a hemorrhage and edema. The number of congested capil­ large number of studies in cellular rejection have accumu­ laries and area of hemorrhage increased and extended to lated. However. the role of preformed lymphocytotoxic the villi with time. These changes in the grafts were antibodies on small bowel transplantation is not yet de­ macroscopically and histopathologically less severe when fined clearly. We reported previously that Lewis rats transplantation was delayed for more than 15 weeks. The sensitized with multiple ACI skin grafts produced a high inflammatory infiltrates of neutrophils and lymphocytes titer of anti-ACI lymphocytotoxic antibodies (IgG > > appeared between 18 and 26 hours after grafting in the IgM) and hyperacutely rejected ACI heart and liver latter specimen. grafts.' We also showed that the survival of either kind of When heart and kidney grafts were transplanted into graft in sensitized recipients inversely correlated to the sensitized recipients more than 15 weeks after skin grafting lymphocytotoxic antibody titer and the length oftime after under FK506 treatment. median graft survivals were 4.5 the last skin grafting. When transplantation was delayed (n = 4) and 3 days (n = 4). respectively. These survival for 15 weeks or more after sensitization. heart and liver times were much shorter than those seen in unsensitized grafts were rejected in an antibody- and cell-mediated recipients both with and without immunosuppression. sug­ fashion. providing a clinically relevant animal model to gesting that irreversible antibody-mediated damage oc­ study the role of preformed Iymphocytotoxic antibodies on curred to these grafts. When live(grafts. which have been transplantation. : known to be resistant to antibody-mediated damage, were In this study. using the same sensitization protocol. transplanted, three of five animals had a prolonged sur­ antibody-mediated small bowel allograft rejection was vival of more than 80 days and two survived for more than studied. Results were compared with those of other organ 100 days. After small bowel grafting in the same condition. allografts in the same setting. three out of five animals died within 5 days: however. the other two survived for more than 100 days. MATERIALS AND METHODS Inbred Lewis (LEW. RTlI) and ACI (RTI") rats were used as DISCUSSION recipients and donors. respectively. LEW rats were sensitized with four successive ACI tail skin grafts at 14-day intervals.' The Although the development of acute cellular rejection fol­ surgical procedure of small bowel transplantation with caval lowing small bowel transplantation was demonstrated. drainage has been described before. l To characterize the his­ antibody-mediated rejection in this transplantation is not topathological changes of antibody-mediated rejection seen in clearly defined. Using a well-established animal model of small bowel grath. ACI intestine was transplanted into sensitized antibody-mediated allograft rejection. humoral rejection of recipients either within 4 weeks In = 2) or more than 15 weeks the small bowel graft was characterized in this study. (n = 3) after the last skin grafting. Serial specimens were taken Typical histopathological changes were capillary conges­ from the graft intestine and lymphoid tissues and processed for tion and hemorrhage seen in lamina propria. submucosa. histopathological analysis. In the following experiments. responses of small bowel graft to and inside the lymphoid tissues of Peyer's patches and preformed antibodies were compared with those of other organ mesenteric lymph nodes. and later in the villi. Similar allografts. Sensitized recipients received either small bowel. findings were observed in one patient who received cross­ heart. kidney. or liver graft from ACI rats more than 15 weeks match positive isolated small bowel graft. Postperfusion after the last skin grafting. FKS06 was given at a dose of 1.0 biopsy of this patient showed capillary congestion and mglkgld for 7 days staning on the day of grafting to avoid acute hemorrhage. which lasted for 2 weeks after transplanta­ cellular rejection. tion. RESULTS From The Pittsburgh Transplant Institute. Departments of Sur­ Macroscopically. small bowel grafts transplanted into sen­ gery and Pathology. University of Pittsburgh, Pittsburgh. Pennsyl· sitized animals within 4 weeks after the last skin graft vania. became dark in color and developed congestion within a Address reprint requests to Thomas E. Starzl. MD. PhD. 3601 few minutes after normal revascularization. During the Fifth Avenue. 5C Falk Clinic. Pittsburgh. PA 15213. next 60 minutes. grafts became completely hemorrhagic. A e: 1994 by Appleton & Lange notable histopathological change seen in these specimens 004",345/94/$3.001+0 Transplantation Proceedings. Vol 26. No 3 (June). 1994: pp 1517-1518 1517 1518 MURASE, FUJISAKI. TANABE ET AL Delayed transplantation to primed animals (> 15 weeks) graft may be more resistant to antibody-mediated damage under FK506 treatment was performed because of the compared to hean and kidney grafts. relevance to the grafting to presensitized patients. In spite of sufficient FK506 treatment. survival times of heart and REFERENCES kidney grafts in sensitized recipients were reduced when I. Furuya T. Murase N. Nakamura K. et al: Hepatology compared to those in unsensitized recipients. Damage to 16:1415. 1992 heart and kidney grafts caused by preformed antibodies 2. Nakamura K. Murase N. Becich M. et al: Am J Pathol may be irreversible. On the other hand. 60% of liver grafts 142: 1383. 1993 and 40% of small bowel grafts showed extended survival of 3. Murase N. Demetris AJ. Kim DG. et al: Surgery 108:880. more than 80 days in the same setting. The small bowel 1990 .
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